Comparison of ELISA protocols measuring HPV16 IgG antibodies and evaluation of the association between HPV16 seropositivity and HPV DNA detection

Bien que les infections cervicales au VPH soient très courantes, la séroconversion ne se produit pas toujours. Nous avons comparé deux protocoles basés sur deux dilutions sériques pour mesurer la séroréactivité du papillomavirus humain (VPH) de type 16 et avons étudié si la présence de l'ADN du VPH était associé à la séropositivité au VPH16. Nous avons également évalué si l'association était influencée par la co-infection avec d’autres types de VPH et par la charge virale. Les données utilisées proviennent de femmes brésiliennes qui ont participées à l'étude de cohorte Ludwig-McGill portant sur l'histoire naturelle de l'infection du col de l’utérus par le VPH. Les protocoles de sérologie étaient basés sur des particules pseudo-virales (VLP) composés par les protéines L1 ou L1 et L2 qui sont, respectivement, les protéines principale et secondaire de la capside virale. Deux dilutions sériques ont aussi été utilisées, soient : 1:10 et 1:50. La séroréactivité au VPH16 a été exprimée en rapports d'absorbance normalisé (NAR). Le génotypage de l'ADN du VPH et la charge virale ont été évalués par des méthodes basées sur la PCR. La corrélation et la concordance entre les dilutions de chaque protocole (VLP L1 et L1+L2) ont été évaluées par la corrélation de Pearson (r) et la méthode de Bland-Altman, respectivement. La performance des différents protocoles a été comparée à l’aide de courbe ROC (receiver operating characteristic) en utilisant la présence de l'ADN de VPH16 comme étalon-or. La régression linéaire a été utilisée pour analyser l'association entre la séropositivité au VPH16 et la détection de l’ADN du VPH avec les deux protocoles. La présence de l’ADN du VPH a été analysée en fonction (1) des types spécifiques de VPH plus ou moins apparentés au VPH16 et (2) l’infection VPH16 détectée seule ou en co-infection avec d’autres types de VPH. Les modèles de régression linéaire présentés ci-haut ont aussi été utilisées sur l’ensemble de la cohorte testée avec le protocole VLP L1+L2 et dilution sérique 1:10. L'impact de l'âge en tant que facteur de confusion potentiel ou modificateur d'effet a été analysé dans ce modèle. Finalement, l’association entre la charge virale de VPH16 et la séroréactivité a été analysée à l’aide de la corrélation de Pearson. L’ampleur des différences de la moyenne des log10-NAR et les écart-types entre les dilutions sériques observées pour chaque protocole (VLP L1 et L1+L2) étaient, respectivement, -0,081 (0,123) et -0,026 (0,150) unités logarithmiques. Les NARs obtenus par les dilutions sériques utilisées (1:10 et 1:50) pour chaque protocole étaient fortement corrélés (r = 0,87 vs. 0,94, respectivement). Cependant, l'utilisation de VLP L1+L2 a augmenté la performance du test à détecter les anticorps IgG anti-VPH16 en particulier avec la dilution sérique 1:10 [l’aire sous la courbe ROC la plus élevée (IC 95%) = 0,7330 (0,6465 – 0,8495)]. Les modèles de régression ont montré que la séroréactivité au VPH16 n’étaient qu’associée à la présence de l’ADN du VPH16 et non pas aux autres types. Par exemple, les analyses avec le protocole VLP L1+L2 et la dilution sérique 1:10 ont montré que la séroréactivité au VPH16 était associée à la présence de l'ADN du VPH16, β (IC 95%) = 0,24 (0,14 – 0,34), et non pas aux VPH31 ou 35, β (IC 95%) = 0.03 (-0,19 – 0,25), ou VPH52, 67, 33 ou 58, β (IC 95%) = 0,15 (-0,04 – 0,34), comparativement aux femmes infectées par tout autre type de VPH ou négative. Les analyses sur la cohorte entière avec le même protocole ont aussi montré que l’association entre la séroréactivité et l’ADN du VPH16 était similaire quand l’infection était présente seule ou en co-infection, β (IC 95%) = 0,14 (0,07 – 0,21) et β (IC 95%) = 0,11 (0,01 – 0,21), respectivement, comparativement à celles infectées par tout autre type de VPH ou négative. L’âge n’a pas été un facteur de confusion important et n’a pas été un modificateur d’effet dans l'analyse de l'ensemble de la cohorte. La charge virale du VPH16 n’a pas été corrélée avec la séroréactivité du VPH16, r (95% IC) = -0,04 (-0,34 – 0,27); β (IC 95%) = -0,01 (-0,08 – 0,06). En conclusion, le protocole le plus fortement corrélé avec l’ADN du VPH-16 a été celui avec le VLP L1+L2 et la dilution sérique 1:10. Seule la présence de l'ADN du HPV16 a été associée à la séropositivité au HPV16 (pas d’autre type de HPV), et elle n'a pas été influencée par la co-infection ou la charge virale.Although cervical HPV infections are very common, seroconversion does not always occur. We compared two protocols based on two serum dilutions to measure human papillomavirus (HPV) type 16 seroreactivity and investigated if HPV DNA positivity was associated with HPV16 seropositivity. We also assessed if the association was influenced by co-infection with other HPV types and viral load. The data used are from Brazilian women participating in the Ludwig-McGill cohort study on the natural history of cervical HPV infection. The serology protocols were based on virus-like particles (VLPs) composed by the L1 or L1 and L2 proteins which are, respectively, the major and minor viral capsid proteins. Two serum dilutions were used: 1:10 and 1:50. HPV16 seroreactivity was expressed as normalized absorbance ratio (NAR). HPV DNA genotyping and viral load were evaluated by PCR-based methods. Correlation and agreement between serum dilutions of each protocol (L1 and L1+L2 VLP) were assessed by Pearson’s correlation (r) and Bland-Altman method, respectively. The performance of the different protocols was compared using the receiver operating characteristic (ROC) curve using the presence of HPV16 DNA as the gold standard. Linear regression was used to analyze the association between HPV16 seropositivity and the detection of HPV DNA infection with both protocols. The presence of HPV DNA was analyzed based on (1) specific HPV types more or less related to HPV16 and (2) HPV16 infection detected alone or in co-infection with other HPV types. The linear regression models presented above were also used on the entire cohort tested with VLP L1+L2 and serum dilution 1:10. The impact of age as a potential confounding factor or effect modifier was analyzed in this model. Finally, the association between HPV16 viral load and seroreactivity was analyzed using Pearson correlation. The magnitude of log10-NARs mean differences between serum dilutions and their standard deviations for each protocol (L1 and L1+L2 VLP) were -0,081 (0.123) and -0.026 (0.150) log units, respectively. The NARs obtained by the serum dilutions used (1:10 and 1:50) for each protocol were strongly correlated (r = 0.87 vs. 0.94, respectively). However, the use of L1+L2 VLPs increased the performance of the test to detect HPV16 IgG antibodies, especially with the 1:10 serum dilution [the highest ROC area (95% CI) = 0.7330 (0.6465 – 0.8495)]. The regression models showed that HPV16 seroreactivity was uniquely associated with the presence of HPV16 DNA and not with other HPV types. For example, the analyses with the protocol L1+L2 VLP and serum dilution 1:10 showed that HPV16 seroreactivity was associated with the presence of HPV16 DNA, β (95% CI) = 0.24 (0.14 - 0.34), and not to HPV31 or 35, β (95% CI) = 0.03 (-0.19 - 0.25), or HPV52, 67, 33 or 58, β (95% CI) = 0.15 (-0.04 - 0.34), compared to women infected with any other HPV type or negative. The analysis of the entire cohort shows that the association between HPV16 seroreactivity and HPV16 DNA infection was similar when the infection was present alone or in co-infection, β (95% CI) = 0.14 (0.07 - 0.21) and β (95% CI) = 0.11 (0.01 - 0.21), respectively, compared to those infected with any other HPV type or negative. Age was not a significant confounder nor an effect modifier in the analysis of the entire cohort. The HPV16 viral load was not correlated with HPV16 seroreactivity, r (95% CI) = -0.04 (-0.34 – 0.27); β (95% CI) = -0.01 (-0.08 – 0.06). In conclusion, the protocol with the higher correlation with HPV 16 positivity was that with the L1+L2 VLP and serum dilution 1:10. Only the presence of HPV16 DNA was associated with HPV16 seropositivity (no other HPV type), and it was not influenced by co-infection or viral load

Stabilizing Consensus with Many Opinions

We consider the following distributed consensus problem: Each node in a complete communication network of size $n$ initially holds an \emph{opinion}, which is chosen arbitrarily from a finite set $\Sigma$. The system must converge toward a consensus state in which all, or almost all nodes, hold the same opinion. Moreover, this opinion should be \emph{valid}, i.e., it should be one among those initially present in the system. This condition should be met even in the presence of an adaptive, malicious adversary who can modify the opinions of a bounded number of nodes in every round. We consider the \emph{3-majority dynamics}: At every round, every node pulls the opinion from three random neighbors and sets his new opinion to the majority one (ties are broken arbitrarily). Let $k$ be the number of valid opinions. We show that, if $k \leqslant n^{\alpha}$, where $\alpha$ is a suitable positive constant, the 3-majority dynamics converges in time polynomial in $k$ and $\log n$ with high probability even in the presence of an adversary who can affect up to $o(\sqrt{n})$ nodes at each round. Previously, the convergence of the 3-majority protocol was known for $|\Sigma| = 2$ only, with an argument that is robust to adversarial errors. On the other hand, no anonymous, uniform-gossip protocol that is robust to adversarial errors was known for $|\Sigma| > 2$

Gold(III)-pyrrolidinedithiocarbamato Derivatives as Antineoplastic Agents

Transition metals offer many possibilities in developing potent chemotherapeutic agents. They are endowed with a variety of oxidation states, allowing for the selection of their coordination numbers and geometries via the choice of proper ligands, leading to the tuning of their final biological properties. We report here on the synthesis, physico-chemical characterization, and solution behavior of two gold(III) pyrrolidinedithiocarbamates (PDT), namely [AuIIIBr2(PDT)] and [AuIIICl2(PDT)]. We found that the bromide derivative was more effective than the chloride one in inducing cell death for several cancer cell lines. [AuIIIBr2(PDT)] elicited oxidative stress with effects on the permeability transition pore, a mitochondrial channel whose opening leads to cell death. More efficient antineoplastic strategies are required for the widespread burden that is cancer. In line with this, our results indicate that [AuIIIBr2(PDT)] is a promising antineoplastic agent that targets cellular components with crucial functions for the survival of tumor cells

Manipulation of Mitochondria Dynamics Reveals Separate Roles for Form and Function in Mitochondria Distribution

Mitochondria shape is controlled by membrane fusion and fission mediated by mitofusins, Opa1, and Drp1, whereas mitochondrial motility relies on microtubule motors. These processes govern mitochondria subcellular distribution, whose defects are emphasized in neurons because of their polarized structure. We have studied how perturbation of the fusion/fission balance affects mitochondria distribution in Drosophila axons. Knockdown of Marf or Opa1 resulted in progressive loss of distal mitochondria and in a distinct oxidative phosphorylation and membrane potential deficit. Downregulation of Drp1 rescued the lethality and bioenergetic defect caused by neuronal Marf RNAi, but induced only a modest restoration of axonal mitochondria distribution. Surprisingly, Drp1 knockdown rescued fragmentation and fully restored aberrant distribution of axonal mitochondria produced by Opa1 RNAi; however, Drp1 knockdown did not improve viability or mitochondria function. Our data show that proper morphology is critical for proper axonal mitochondria distribution independent of bioenergetic efficiency. The health of neurons largely depends on mitochondria function, but does not depend on shape or distribution. Trevisan et al. separate the independent contribution of form and function in determining the distribution of mitochondria in axons. They show that morphology is crucial for proper axonal mitochondria distribution, independent of their bioenergetic efficiency. However, the health of neurons depends on mitochondria function, but does not depend on shape or distributio

Simple Dynamics for Plurality Consensus

We study a \emph{Plurality-Consensus} process in which each of $n$ anonymous agents of a communication network initially supports an opinion (a color chosen from a finite set $[k]$). Then, in every (synchronous) round, each agent can revise his color according to the opinions currently held by a random sample of his neighbors. It is assumed that the initial color configuration exhibits a sufficiently large \emph{bias} $s$ towards a fixed plurality color, that is, the number of nodes supporting the plurality color exceeds the number of nodes supporting any other color by $s$ additional nodes. The goal is having the process to converge to the \emph{stable} configuration in which all nodes support the initial plurality. We consider a basic model in which the network is a clique and the update rule (called here the \emph{3-majority dynamics}) of the process is the following: each agent looks at the colors of three random neighbors and then applies the majority rule (breaking ties uniformly). We prove that the process converges in time $\mathcal{O}( \min\{ k, (n/\log n)^{1/3} \} \, \log n )$ with high probability, provided that $s \geqslant c \sqrt{ \min\{ 2k, (n/\log n)^{1/3} \}\, n \log n}$. We then prove that our upper bound above is tight as long as $k \leqslant (n/\log n)^{1/4}$. This fact implies an exponential time-gap between the plurality-consensus process and the \emph{median} process studied by Doerr et al. in [ACM SPAA'11]. A natural question is whether looking at more (than three) random neighbors can significantly speed up the process. We provide a negative answer to this question: In particular, we show that samples of polylogarithmic size can speed up the process by a polylogarithmic factor only.Comment: Preprint of journal versio

Urinary levels of free 2,5-hexanedione in Italian subjects non-occupationally exposed to n-hexane

The purpose of the study is to evaluate the urinary levels of free 2,5-hexanedione (2,5-HD) in Italian subjects non-occupationally exposed to n-hexane, in order to define background values in non-occupational settings. The study was carried out on 99 subjects of the general population. The analysis of free 2,5-HD was performed by gas chromatography-mass spectrometry. Personal information about the subjects was ascertained by means of a self-administered questionnaire. The urinary levels of free 2,5-HD were in the range of <12.0\u201377.9 g/L (5th\u201395th percentiles). The urinary excretion of the metabolite did not seem to be influenced by gender, age, smoking habit or area of residence. Statistically significant dierences (p = 0.03) were found between the free 2,5-HD urinary levels according to the vehicular trac intensity within the area of residence and to body mass index of subjects. The background levels of free 2,5-HD found in this study could contribute to the definition of reference values of general population non-occupationally exposed and could be useful to the toxicologists and industrial hygienists to determine whether workers have been exposed to higher levels of n-hexane than the general population

Cooperativas, una alternativa de alivio en épocas de crisis

Con la intención de contribuir a discernir en nuestro país el conocimiento del potencial que disponen las empresas cooperativas a la hora de contribuir al alivio de la pobreza mediante la creación de empleo y la satisfacción de necesidades físicas básicas de la sociedad, con una mayor eficacia y eficiencia que las empresas conocidas, he emprendido este trabajo de investigación, planteándome como objetivo general describir las características de funcionamiento que posee ésta institución y analizarla en función de su naturaleza. Motivada por el contexto económico de crisis constante que caracteriza a mi país aspiro a obtener un dominio acabado del tema para poder brindar un correcto asesoramiento, tarea propia del profesional en Ciencias Económicas y aportar algunos aspectos sobre el cooperativismo entendiendo a éste como la combinación de elementos sociales y económicos que sin dudas tendrá una importancia cada vez mayor debido a que la ayuda mutua y la solidaridad activa podrán contribuir a una mejor calidad de vida, a un ambiente más hospitalario, más ameno, más tolerable para permitir una vivencia económica más equitativa, enfoque que es coincidente en el plano internacional y en el del derecho comparado en particular

Bond Percolation in Small-World Graphs with Power-Law Distribution

Full-bond percolation with parameter p is the process in which, given a graph, for every edge independently, we keep the edge with probability p and delete it with probability 1-p. Bond percolation is studied in parallel computing and network science to understand the resilience of distributed systems to random link failure and the spread of information in networks through unreliable links. Moreover, the full-bond percolation is equivalent to the Reed-Frost process, a network version of SIR epidemic spreading. We consider one-dimensional power-law small-world graphs with parameter ? obtained as the union of a cycle with additional long-range random edges: each pair of nodes {u,v} at distance L on the cycle is connected by a long-range edge {u,v}, with probability proportional to 1/L^?. Our analysis determines three phases for the percolation subgraph G_p of the small-world graph, depending on the value of ?. - If ? < 1, there is a p < 1 such that, with high probability, there are ?(n) nodes that are reachable in G_p from one another in ?(log n) hops; - If 1 < ? < 2, there is a p < 1 such that, with high probability, there are ?(n) nodes that are reachable in G_p from one another in log^{?(1)}(n) hops; - If ? > 2, for every p < 1, with high probability all connected components of G_p have size ?(log n)